Methylation and mRNA expression of ADRA1A gene in hepatocellular carcinoma and its clinical significance
Objective To investigate the methylation status and mRNA expression of adrenergic receptor alpha 1A(ADRA1A)gene in hepatocellular carcinoma(HCC),and analyze its clinical significance.Methods ADRA1A information was queried from TCGA dataset,and the data were analyzed using cBioPortal,Gene Expression Omnibus and GEPIA online public data.Kaplan-Meier-plotter in the GEPIA dataset was used to analyze the effect of ADRA1A relative expression on overall survival(OS).A total of 90 HCC patients admitted to the Second Hospital of Hebei Medical University from March 2017 to November 2018 were collected.Real-time quantitative fluorescent PCR(qPCR)was used to determine the expression of ADRA1A in HCC tissues and adjacent tissues,and methylation-specific polymerase chain reaction(MSP)was used to detect the methylation status of ADRA1A.The efficacy of ADRA1A gene expression in the diagnosis of HCC was evaluated by receiver operating characteristic curve(ROC).The survival curves was drawed by Kaplan-Meier.Cox proportional regression model was used to analyze the prognostic factors of HCC patients.Results The TCGA database analysis showed that ADRA1A was a methylated gene in the adrenergic receptor in HCC,and the survival of patients with high expression of ADRA1A was significantly improved.The relative expression level of ADRA1A in HCC tissues was significantly lower than that in paracancer tissues[0.63(0.31,1.07)vs.0.96(0.85,1.17),P＜0.001].ROC curve results showed that the area under curve(AUC)of ADRA1A gene expression level differentiating HCC and paracancer tissues was 0.702(0.619-0.785).The methylation rate of ADRA1A in HCC tissues was significantly higher than that in paracancer tissues(47.78％vs.23.33％,P=0.001).The expression of ADRA1A in HCC tissues was significantly lower in patients with ADRA1A methylation than that in patients with ADRA1A non-methylation[0.39(0.16,0.72)vs.0.93(0.55,1.55),P＜0.001].The methylation of ADRA1A was only associated with UICC stage(P＜0.05).Kaplan-Meier analysis showed that the median OS of ADRA1A non-methylated patients was not reached,which was significantly higher than that of ADRA1A methylated patients at 13.0 months(6.5-19.4 months),and the difference was statistically significant(P＜0.05).Multivariate Cox model results showed that ADRA1A methylation and AFP were independent factors affecting OS in HCC patients(P＜0.05).Conclusion Hypermethylation of ADRA1A gene may be an effective diagnostic and prognostic marker for HCC.
万方数据
维普
